SciLifeLab Uppsala launches demonstration projects

“In relatively small projects we will be testing new ideas and technologies and will then expand those that prove to have the greatest potential. At the core of the projects is what we call the SciLife spirit, that is, creative collaborations between different research competencies surrounding the large-scale technology that is available in SciLifeLab,” says Professor Kerstin Lindblad-Toh, research director at SciLifelab Uppsala, which, together with SciLifeLab Stockholm, has the ambition of becoming one of the world’s leading research laboratories in life sciences.

SciLifeLab Uppsala is a strong research environment at Uppsala University that, together with scientists in Stockholm, garnered the government’s strategic research grant in molecular bioscience last year.  Six demonstration projects have now been selected to receive between SEK 350 000 and SEK 700 000 to test new ideas and technologies. The idea is that those relatively small projects that show the greatest potential will then be expanded. The projects were singled out by independent experts in the field, based on some 25 applications.

SciLifeLab Uppsala collaborates with its equivalent in Stockholm, SciLifeLab Stockholm.

For more information, please contact Research Director Kerstin Lindblad-Toh, mobile: +46 (0)70-324 23 36 or kerstin.lindblad-toh@imbim.uu.se

The demonstration projects in brief:

Chromatin regulatory RNAome in normal and cancer cells
Research leader: Chandra Kanduri, Department of Genetics and Pathology, Rudbeck Laboratory.

Nearly 99 percent of human genes consist of non-coding RNA molecules, that is, they do not give rise to proteins. On the other hand, these molecules do have a function as RNA. The function of thousands of recently discovered non-coding RNA molecules is largely unknown today. Now research both from the Uppsala group and from other laboratories indicates that long non-coding RNA regulates various key biological functions with the aid of chromatin. Ongoing research also suggests that non-coding RNA can also stimulate cancer metastases by reprogramming the chromatin structure. Within the framework of the demonstration project, the Uppsala scientists, who recently characterized more than 200 functional non-coding RNAs in humans via a new technology, will continue to study the importance of these molecules in cancer cells and stem cells in different model organisms.

“By combining advanced technology with studies of model organisms, we hope to be able to understand what role non-coding RNA plays both in normal development and in diseases,” says Chandrasekhar Kanduri.

More about research in Chandra’s [DSM1] group: http://www.genpat.uu.se/en//node228


Sequencing Bacterial Genomes in 96 Microtitre Formats
Research leader: Siv Andersson, Section for Molecular Evolution, Center for Evolutionary Biology.

In May billions of Russian aphides blew across the Baltic Sea. This project will study the genetic make-up of bacteria that exist in aphides and other insects. The aim is to develop techniques to map the genes of bacteria on a very large scale on the basis of extremely small amounts of DNA. A total of 96 bacterial genomes will be mapped from 96 individual insects in a single experiment.
“In the future this can enable global studies of the dispersion routes for pathogenic bacteria on a large scale and indicate changes in their genes that might lead to new epidemics,” says Siv Andersson.
More about research in Andersson’s group: http://www.egs.uu.se/molev/staff/siv_a_rea.html


Mechanisms and biological roles of bacterial regulatory RNAs: Global effects and involvement of helper protein
Research leader: Gerhart Wagner, Department of Cell and Molecular Biology, BMC.

Regulatory RNA in bacteria and associated proteins are the theme of the group’s project. These RNAs govern physiological properties such as stress endurance in bacteria, but also their pathogenic capacity. The project will make use of large-scale sequencing in order to understand the enigmatic mechanism that bestows acquired immunity to bacterial viruses – in a way that is similar to immunity in mammals. This mechanism is fundamental to the evolutionary struggle – or arms race – between bacteria and viruses. A new method of mutation analysis will also be developed, based on millions of individual mutations to be charted.
More about research in Wagner’s group: http://www.urrc-linnaeuscentre.uu.se/about.html


Whole genome sequencing of monozygotic twins
Research leader: Lars Feuk, Department of Genetics and Pathology, Rudbeck Laboratory.

Identical twins are regarded as having identical sets of genes. Nevertheless, there are many examples where one of the twins contracts a disease that is genetically determined, while the other twin does not present any symptoms. Possible explanations for this may be that there are genetic changes either in early embryonic development or in connection with the formation of specific tissues, entailing that the genetic differences only exist in certain cells in the body. Alternatively, the disease may be caused by an interaction between a genetic factor and an environmental factor that only one of the twins was exposed to. Using new technologies it is now possible to test the first two hypotheses by reading the entire genome.
“In our project we will therefore be sequencing the entire genome from a pair of identical twins, and we will do this in two different tissues from each twin. If genetic differences can be detected, it will mean that it would be possible to find genes involved in various diseases,” says Lars Feuk.
More about research in Feuk’s group: http://www.genpat.uu.se/en//node560


Somatic genetic variation in asthma: disease diagnostics, biomarker and drug discovery
Research leader: Jan Dumanski, Department of Genetics and Pathology, Rudbeck Laboratory.

We know today that different cells in the body of one and the same individual are not genetically identical. Differences in genes arise throughout life and can be identified with the help of modern technology. The scientists’ hypothesis is that this type of variation is important in the emergence of asthma, which affects about 10 percent of the population – that there are minor genetic changes in genes in lymphocytes in the blood of asthma patients, compared with connecting tissue cells from the same individual. The aim of the project is to find links between genetic and epigenetic differences in asthma patients with two well-defined subtypes of asthma: allergic and non-allergic asthma. The researchers will also be studying pairs of identical twins who differ in terms of their asthma status, where one is healthy and the other has the condition.
“Our goal is to characterize new genetic asthma-specific changes that can be exploited for enhanced diagnosis or treatment of asthma patients,” says Jan Dumanski.
More about research in Dumanski’s group: http://www.genpat.uu.se/en//node135


Analyses of the genetic determinants of the plasma proteome
Research leader: Jonas Bergquist, Department of Physical and Analytical Chemistry.

Using high-resolution fluid chromatography and mass spectrometry, the research group will perform a unique characterization of the proteins in plasma. The idea is to try to distinguish as many components as possible and measure their amounts (without necessarily being able to identify all of them). The measurements will be undertaken in a large population (some 700 individuals who all come from a single large genealogical tree) whose genes have been mapped. These analyses represent a kind of mapping of the connection between plasma proteins and the parts of our genes that affect them.
“This has the potential to become an extremely important tool for further studies of biomarkers for our most common public health diseases and to open entirely new pathways in the field of medical research,” says Jonas Bergquist.
More about research in Bergquist’s group: http://www.analytisk.kemi.uu.se/eng/research/index.shtm